Dietary cholesterol induces in the guinea pig a hemolytic anemia preceded by fatty infiltration of the liver, by increases in liver, plasma and erythrocyte (RBC) cholesterol contents, by changes in the type of plasma lipoproteins and their apoprotein profile, and by changes in RBC morphology. We propose to study: 1) the role of the abnormal lipoproteins in the net accumulation of cholesterol by the red cell membrane in vivo and in vitro; 2) the mechanism(s) by which the increased cholesterol content causes the morphological abnormalities of the red cell; and 3) the possible involvement of the immune system in the development of the hemolytic anemia.